Facilitated Diffusion of Proteins on Chromatin: We present a theoretical model of facilitated diffusion of proteins in the cell nucleus. This model, which takes into account the successive binding and unbinding events of proteins to DNA, relies on a fractal description of the chromatin which has been recently evidenced experimentally. Facilitated diffusion is shown quantitatively to be favorable for a fast localization of a target locus by a transcription factor and even to enable the minimization of the search time by tuning the affinity of the transcription factor with DNA. This study shows the robustness of the facilitated diffusion mechanism, invoked so far only for linear conformations of DNA.
Intracellular Facilitated Diffusion: Searchers, Crowders, and Blockers: In bacteria, regulatory proteins search for a specific DNA-binding target via “facilitated diffusion”: a series of rounds of three-dimensional diffusion in the cytoplasm, and one-dimensional (1D) linear diffusion along the DNA contour. Using large scale Brownian dynamics simulations we find that each of these steps is affected differently by crowding proteins, which can either be bound to the DNA acting as a road block to the 1D diffusion, or freely diffusing in the cytoplasm. Macromolecular crowding can strongly affect mechanistic features such as the balance between three-dimensional and 1D diffusion, but leads to surprising robustness of the total search time.
The lac Repressor Displays Facilitated Diffusion in Living Cells: Transcription factors (TFs) are proteins that regulate the expression of genes by binding sequence-specific sites on the chromosome. It has been proposed that to find these sites fast and accurately, TFs combine one-dimensional (1D) sliding on DNA with 3D diffusion in the cytoplasm. This facilitated diffusion mechanism has been demonstrated in vitro, but it has not been shown experimentally to be exploited in living cells. We have developed a single-molecule assay that allows us to investigate the sliding process in living bacteria. Here we show that the lac repressor slides 45 ± 10 base pairs on chromosomal DNA and that sliding can be obstructed by other DNA-bound proteins near the operator. Furthermore, the repressor frequently (>90%) slides over its natural lacO1 operator several times before binding. This suggests a trade-off between rapid search on nonspecific sequences and fast binding at the specific sequence.
In Vivo Facilitated Diffusion Model: Under dilute in vitro conditions transcription factors rapidly locate their target sequence on DNA by using the facilitated diffusion mechanism. However, whether this strategy of alternating between three-dimensional bulk diffusion and one-dimensional sliding along the DNA contour is still beneficial in the crowded interior of cells is highly disputed. Here we use a simple model for the bacterial genome inside the cell and present a semi-analytical model for the in vivo target search of transcription factors within the facilitated diffusion framework. Without having to resort to extensive simulations we determine the mean search time of a lac repressor in a living E. coli cell by including parameters deduced from experimental measurements. The results agree very well with experimental findings, and thus the facilitated diffusion picture emerges as a quantitative approach to gene regulation in living bacteria cells. Furthermore we see that the search time is not very sensitive to the parameters characterizing the DNA configuration and that the cell seems to operate very close to optimal conditions for target localization. Local searches as implied by the colocalization mechanism are only found to mildly accelerate the mean search time within our model.
My botty best at summarizing from Wikipedia: facilitated diffusion is the process of spontaneous passive transport of molecules or ions across a biological membrane . molecules and ions move down their concentration gradient reflecting its diffusive nature . transport relies on molecular binding between cargo only small, non-polar molecules can diffuse easily across the membrane . no nonpolar molecules are transported by proteins in the form of transmembrane channels . facilitated transport depends on the presence of an activated binding event non-polar molecules, such as retinol or lipids, are poorly soluble in water . they are transported through aqueous compartments of cells or through extracellular space by water-soluble carriers . only permease changes its shape in order to transport metabolites . group translocation transportation is a form of transport through a cell membrane . glucose, sodium ions, and chloride ions must engineers have attempted to mimic the process of facilitated transport in synthetic membranes . but they have met with limited success to date due to poor carrier stability . facilitated diffusion is one form of diffusion and it is important in several metabolic processes in vitro and in vivo are similar in that the association and dissociation rates of TF’s to and from the DNA are similar . in prokaryotic bacteria cells such as E. coli, facilitated according to Brackley et al. (2013), the protein searches the entire length of the DNA chain using 3-D and 1-D diffusion patterns . the high incidence of Crowder proteins creates an osmotic pressure in eukaryotes, facilitated diffusion occurs in the nucleoplasm on chromatin filaments . oxygen affinity with hemoglobin on red blood cell surfaces enhances bonding ability . this mechanism of facilitated diffusion of oxygen by hemoglobin or myoglobin was discovered and initiated by Wittenberg and Scholander . they carried out experiments to test for the steady-state of diffusion at various pressures . hemoglobin increases the rate of constant diffusion of oxygen . facilitated diffusion occurs when oxyhemoglobin molecule is randomly displaced . carbon monoxide has a dissociation velocity which is 100 times less than glucose diffuses across membranes through facilitated diffusion, down concentration gradient . since glucose is a large molecule, it is difficult to be transported across the membrane through simple diffusion . Facilitated diffusion helps in the release of accumulated glucose into the extracellular space adjacent to the blood capillary.
